Calcium homeostasis and compartmentation in liver.

Abstract

In recent years it has become increasingly apparent that changes of intracellular free Ca2+ exert a vital role as a transducing agent for the mediation of chemical events linking hormonal or other external stimulae to alterations of intracellular enzyme activities (Rasmussen and Goodman, 1977; Kretzinger, 1976; Bygrave, 1978). With liver, which has a low resting membrane potential and flux of Ca2+ across the plasma membrane, it has been suggested that α-adrenergic agents elicit a release of Ca2+ from intracellular storage sites, and a flux of Ca2+ between intracellular organelles and Ca2+ binding target proteins (Keppens et al., 1977; Blackmore and Exton, 1977; Chen et al., 1978; Exton, 1979). Thus, α-adrenergic activity in liver is thought to be mediated by cyclic AMP independent processes and to involve a direct increase of phosphorylase b kinase activity by a rise of intracellular free Ca2+ concentration from about 10−7 M to about 10−6 M (Exton, 1979; Khoo and Steinberg, 1975; Shimazo and Amakawa, 1975; Van de Werve et al., 1977). Although there is a considerable body of data concerning the effects of catecholamines, glucagon and other hormones on 45Ca2+flux in liver (Chen et al., 1978; Foden and Randle, 1978; Blackmore et al., 1979; Blackmore et al., 1978), a more detailed understanding of the sequence and molecular mechanisms of the events involved in these processes has been severely hampered by a lack of knowledge of the intracellular free Ca2+ concentration and calcium compartmentation within the cell.